Acetic Anhydride → (5-(Benzyloxy)pyridin-2-yl)methanol

HRID 640400Notes

Reaction equation

HRID 640400 reaction equation
C(OC(=O)C)(=[O:3])C.[CH2:8]([O:15][C:16]1[CH:17]=[CH:18][C:19]([CH3:23])=[N+:20]([O-])[CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:8]([O:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:23][OH:3])=[N:20][CH:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 123972525-Benzyloxy-2-methylpyridine 1-oxide

Product 1

HCID 11736050(5-(Benzyloxy)pyridin-2-yl)methanolYield 54%

Conditions

Temperature
120 °C

Procedure

To a methylene chloride (100 mL) solution of 5-benzyloxy-2-methyl-pyridine (5.99 g, 30.1 mmol) described in Manufacturing Example 127-1-1 was added m-chloroperbenzoic acid (8.79 g, 33.1 mmol, purity: 65%) at 0° C., which was stirred for 2 hours at room temperature. Saturated aqueous sodium bicarbonate was added to the reaction mixture at 0° C., which was extracted with methylene chloride. The organic layer was separated, washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain 5-benzyloxy-2-methyl-pyridine-1-oxide (7.71 g). Acetic anhydride (77 mL) was added to 5-benzyloxy-2-methyl-pyridine-1-oxide (7.71 g) thus obtained, which was stirred for 80 minutes at 120° C. This mixture was cooled to room temperature and then concentrated under a reduced pressure. To an ethanol (50 mL) solution of this residue was added a 5 N sodium hydroxide aqueous solution (7 mL), which was stirred for 50 minutes at room temperature. The reaction mixture was concentrated under a reduced pressure. The residue was partitioned into saturated aqueous sodium chloride and ethyl acetate. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (4.17 g, 54%).

Workup

  1. customthus obtained
  2. temperatureThis mixture was cooled to room temperature
  3. concentrationconcentrated under a reduced pressure
  4. additionTo an ethanol (50 mL) solution of this residue was added a 5 N sodium hydroxide aqueous solution (7 mL), which
  5. stirringwas stirred for 50 minutes at room temperature
  6. concentrationThe reaction mixture was concentrated under a reduced pressure
  7. customThe residue was partitioned into saturated aqueous sodium chloride and ethyl acetate
  8. customThe organic layer was separated
  9. washwashed with saturated aqueous sodium chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under a reduced pressure
  13. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-9099aceef84c45b0a389261e7da6d2e6
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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